Managed Care - December 2008 - (Page 43)

mately 12.5 mg. Other H-1 receptor antagonists such as dimenhydrinate (Dramamine) or diphenhydramine (Benadryl) are sometimes prescribed and are generally considered safe and effective (Codero 1981, Mitchell 1983). The phenothiazines, like antihistamines, are generally safe and effective for use in pregnancy (Leathem 1986). The most commonly prescribed drug in this class is promethazine (Phenergan). Studies have failed to indicate an increased risk for major malformations. Significant therapeutic benefit has been confirmed by well-assigned randomized controlled trials of various phenothiazines (Briggs 1999, Seto 1997). Promethazine is considered a second or third line agent, and it may be added to pyridoxine/doxylamine per the Society of Obstetricians and Gynecologists of Canada (SOGC) and ACOG guidelines (Aresenault, MY 2002). Metoclopramide use is safe for the management of NVP, although extrapyramidal side effects can be alarming (Berkovitch 2000, Sorenson 2000). Evidence of efficacy is limited even though the drug is frequently prescribed. Metoclopramide is an upper gastrointestinal motility stimulant. Its effectiveness in the treatment of NVP has not been supported by a randomized controlled trial (RCT). Observational trials using home subcutaneous therapy for HG suggested that metoclopramide is safe, effective and economical (Buttino 1998, Buttino 2000, Buttino 2000, Lombardi 2004). An extensive review of the body of evidence regarding continuous subcutaneous antiemetics will be addressed separately because of the unique method of administration, length of stay, and resultant cost. The 5-HT antagonists, such as ondansetron, have recently been used for the treatment of NVP (World 1993). Limited safety data are available on ondansetron, with three case reports and a randomized clinical trial of 15 exposures demonstrating no fetal risk (Mazzotta 2000). Little evidence is available on the effectiveness of the drug for the treatment of NVP. In one study, ondansetron administered intravenously did not show a statistical difference in effectiveness over promethazine, yet it is significantly more expensive (Sullivan 1996). Because of data showing limited effectiveness and because of the expense, ondansetron should not be used as a first-line treatment. Use should be reserved until agents with established safety and effectiveness have been tried and failed. Indeed, ACOG recommends ondansetron as a last resort for women who are dehydrated with symptoms not relieved by other recommended treatments (ACOG 2004). Over the last 18 years, the concept of subcutaneous continuous administration of antiemetic drugs has been promoted to the obstetric community and reimbursed by some health plans, but both metoclopramide and ondansetron for the treatment of NVP are considered “off label use” by the United States Food and Drug Administration. While the concept seems reasonable, just as intravenous nutritional therapy does by bypassing the gut, the body of evidence on this treatment option has never been consolidated and critically reviewed. This article discusses the medical evidence for both continuous subcutaneous ondansetron and metoclopramide delivered by way of an ambulator y pump designed and approved by the FDA for delivering insulin. Health plans utilizing evidencebased guidelines can help ensure that limited health care dollars are spent on proven lower cost options of treatment instead of expensive, unproven, ineffective, or potentially unsafe treatments. Subcutaneous metoclopramide The entire body of evidence on continuous subcutaneous metoclopramide consists of four industrysponsored level III descriptive case series (Buttino 1998, Buttino 2000, Buttino 2000, Lombardi 2004). The first published peer reviewed observational trial was published in 1998 and contained 301 patients who received continuous subcutaneous metoclopramide at home. Results were encouraging with 64.8% of patients obtaining symptom resolution while 24.9% discontinued therapy because of side effects or worsening symptoms. Eleven patients experienced extrapyramidal side effects. Authors reported that the therapy cost $265 per day compared to $1,370 per day in the hospital with the same diagnosis related group (DRG) (Buttino 1998). The second industry-sponsored peer reviewed level III descriptive case series published on home subcutaneous metoclopramide therapy, in 2000, contained a total of 646 patients diagnosed with hyperemesis gravidarum. The data included the patients’ weight at start and stop of treatment, frequency of symptom resolution, and medication side effects. The study concluded that 63.9% of the women had complete resolution of symptoms while 30.5% suffered at least one side effect of treatment. Authors concluded that continuous subcutaneous metoclopramide appeared to be an effective and safe treatment. Authors also inferred that this therapy “may result in decreased cost compared with inpatient hospitalization.” (Buttino 2000). A third report appeared in the form of a book chapter that reported on the 301 patients in the original trial (group 1) compared to the previously published 646 patients in the second trial plus an additional 207 patients (group 2). Noteworthy is the fact that 12.3% of patients in group 2 experienced extrapyramidal side ef- DECEMBER 2008 / MANAGED CARE 43

Table of Contents Feed for the Digital Edition of Managed Care - December 2008

Managed Care - December 2008 Editor's Memo Contents Legislation & Regulation News and Commentary Medication Management Compensation Monitor ICD-10 Offers Huge Opportunity, Challenge Part D at a Crossroads Plans Can Weather the Financial Crisis DM vs. Medical Home? Tackle Prediabetes Reasonable Approach to Morning Sickness Formulary Files Tomorrow's Medicine Outlook

Managed Care - December 2008

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